O243	Localisation of coagulation proteins within the arterial vessel wall in relation to progression of atherosclerosis.
1P.Kaššák, 2S.Heeneman, 3M.Verluyten, 2M.J.A.P.Daemen, 3H.M.H.Spronk, 3H.ten Cate
1Department of Biophysics and Chemical Physics, Comenius University, Bratislava, SK; 2Department of Pathology, Cardiovascular Research Institute Maastricht, University of Maastricht, Maastricht, NL; 3Laboratory of clinical Thrombosis and Hemostasis, Department of Internal Medicine, Cardiovascular Research Institute Maastricht, University of Maastricht, Maastricht, NL.

Introduction: The thrombogenicity of an atherosclerotic plaque depends, at least in part, on the quantitative and qualitative amounts of tissue factor and other coagulation factors expressed by various cell types in the arterial vessel wall. Recently, the presence and expression of tissue factor (TF) and factor VII (FVII) in human atherosclerotic plaques was shown. It is not yet known whether other coagulation factors like prothrombin and factor X (FX), are synthesized by arterial cells and if they contribute to the thrombogenicity of atherosclerotic plaques. To demonstrate the presence of coagulation proteins and to link them to thrombogenicity of atherosclerotic plaques, we studied lesions characterized by intimal thickening, advanced atheroma or thrombosis, by immunohistological staining. Results: In arterial vessels characterized by intimal thickening, TF was demonstrated in association with medial and intimal smooth muscle cells (SMCs), as well as with endothelial cells (ECs) of the vasa vasorum. FVII and FX were cytoplasmic localized in medial SMCs and in association with ECs of the vasa vasorum. Furthermore, FX was also present in fat cells of the adventitia, intimal macrophages and SMCs, and luminal ECs. Thrombin staining was most intense in the extracellular matrix of both adventitia and media. In advanced atheromas, TF and FVII colocalized in association with SMCs located in intima and media, macrophages in intima and adventitia, and ECs of the vasa vasorum. FX was localized in the vasa vasorum and in the shoulder of advanced atheromas (both macrophages and SMCs). Thrombin was demonstrated in the extracellular matrix of the necrotic core of the plaque. In thrombotic lesions, macrophages, polymorphonuclear leukocytes, and ECs contained TF. FVII was localized in SMCs of plaque cap shoulder region, in macrophages, T cells, luminal and neovascular ECs inside the plaque. FX and thrombin were present in association with the extracellular matrix of media and intima. Conclusions: Co-localization of TF, FVII and FX on macrophages and SMC suggests the presence of procoagulant complexes in all stages of atherosclerosis. The localized presence of these procoagulant proteins suggests that they contribute to thrombin generation. In addition to being determinants in thrombogenicity, these proteins may be involved in other pathophysiological processes like cell migration and inflammation.

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